rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2000-12-13
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pubmed:databankReference |
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289841,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289842,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289843,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289844,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289845,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289846,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289847,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289848,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289849,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289850,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289851,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289852,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289853,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289854,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289855,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289856,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289857
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pubmed:abstractText |
Triple-A syndrome (MIM 231550; also known as Allgrove syndrome) is an autosomal recessive disorder characterized by adrenocorticotropin hormone (ACTH)-resistant adrenal insufficiency, achalasia of the oesophageal cardia and alacrima. Whereas several lines of evidence indicate that triple-A syndrome results from the abnormal development of the autonomic nervous system, late-onset progressive neurological symptoms (including cerebellar ataxia, peripheral neuropathy and mild dementia) suggest that the central nervous system may be involved in the disease as well. Using fine-mapping based on linkage disequilibrium in North African inbred families, we identified a short ancestral haplotype on chromosome 12q13 (<1 cM), sequenced a BAC contig encompassing the triple-A minimal region and identified a novel gene (AAAS) encoding a protein of 547 amino acids that is mutant in affected individuals. We found five homozygous truncating mutations in unrelated patients and ascribed the founder effect in North African families to a single splice-donor site mutation that occurred more than 2,400 years ago. The predicted product of AAAS, ALADIN (for alacrima-achalasia-adrenal insufficiency neurologic disorder), belongs to the WD-repeat family of regulatory proteins, indicating a new disease mechanism involved in triple-A syndrome. The expression of the gene in both neuroendocrine and cerebral structures points to a role in the normal development of the peripheral and central nervous systems.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Nov
|
pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:BégeotMM,
pubmed-author:BakiriFF,
pubmed-author:BrottierPP,
pubmed-author:CattolicoLL,
pubmed-author:ChaouachiBB,
pubmed-author:ChaussainJ LJL,
pubmed-author:Hadj-RabiaSS,
pubmed-author:LyonnetSS,
pubmed-author:MugnierCC,
pubmed-author:MunnichAA,
pubmed-author:NavilleDD,
pubmed-author:NicolinoMM,
pubmed-author:PenetCC,
pubmed-author:SalomonRR,
pubmed-author:Tullio-PeletAA,
pubmed-author:WeissenbachJJ,
pubmed-author:de LaetM HMH
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pubmed:issnType |
Print
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
332-5
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11062474-Abnormalities, Multiple,
pubmed-meshheading:11062474-Adrenal Insufficiency,
pubmed-meshheading:11062474-Africa, Northern,
pubmed-meshheading:11062474-Amino Acid Motifs,
pubmed-meshheading:11062474-Amino Acid Sequence,
pubmed-meshheading:11062474-Chromosomes, Artificial, Bacterial,
pubmed-meshheading:11062474-Chromosomes, Human, Pair 12,
pubmed-meshheading:11062474-Codon,
pubmed-meshheading:11062474-Consanguinity,
pubmed-meshheading:11062474-DNA Mutational Analysis,
pubmed-meshheading:11062474-Esophageal Achalasia,
pubmed-meshheading:11062474-Evolution, Molecular,
pubmed-meshheading:11062474-Expressed Sequence Tags,
pubmed-meshheading:11062474-Genes,
pubmed-meshheading:11062474-Haplotypes,
pubmed-meshheading:11062474-Humans,
pubmed-meshheading:11062474-Linkage Disequilibrium,
pubmed-meshheading:11062474-Molecular Sequence Data,
pubmed-meshheading:11062474-Nerve Tissue Proteins,
pubmed-meshheading:11062474-Nervous System Diseases,
pubmed-meshheading:11062474-Nuclear Pore Complex Proteins,
pubmed-meshheading:11062474-Pedigree,
pubmed-meshheading:11062474-Point Mutation,
pubmed-meshheading:11062474-Proteins,
pubmed-meshheading:11062474-Repetitive Sequences, Amino Acid,
pubmed-meshheading:11062474-Sequence Alignment,
pubmed-meshheading:11062474-Sequence Homology, Amino Acid,
pubmed-meshheading:11062474-Species Specificity,
pubmed-meshheading:11062474-Syndrome,
pubmed-meshheading:11062474-Xerophthalmia
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pubmed:year |
2000
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pubmed:articleTitle |
Mutant WD-repeat protein in triple-A syndrome.
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pubmed:affiliation |
Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393, Paris, France.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|